Non-Syndromic Monogenic Obesity via the PCSK1 Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
15189 PCSK1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
15189PCSK181479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

The non-syndromic form of monogenic obesity is a group of single gene disorders with obesity as an isolated or predominant feature. Clinical features include severe early-onset obesity, hyperphagia, increased linear growth, delayed puberty, preserved reproductive function, hypocortisolemia and hyperinsulinemia (Albuquerque et al. 2015; Pigeyre et al. 2016).

Genetics

The non-syndromic form of monogenic obesity was originally considered to be due to homozygous or compound heterozygous deleterious variants in causative genes, but heterozygous loss-of-function variants in these genes have been also widely reported to result in obesity, some of which can be incompletely penetrant (Albuquerque et al. 2015; Pigeyre et al. 2016). Known causative genes encode proteins in the leptin–melanocortin signaling pathway present in the hypothalamus with roles in regulation of food intake and energy expenditure.

The PCSK1 gene (14 coding exons) encodes pro-protein convertase subtilisin/kexin type 1, which acts in the pathway of post-translational processing of prohormones and neuropeptides. So far, documented genetic defects of PCSK1 include missense, splicing, nonsense, small deletion/insertions and large deletions (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

In a study of 845 non-consanguineous extremely obese European subjects, eight heterozygous PCSK1 rare nonsynonymous variants were found in eight unrelated individuals (0.95%), which probably explained obesity attributed to partial prohormone convertase 1 deficiency (Creemers et al. 2012).

Large deletions have been reported involving the PCSK1 gene, but are relatively uncommon (Human Gene Mutation Database).

Testing Strategy

This test is performed using Next-Generation sequencing with additional Sanger sequencing as necessary.

This test provides full coverage of all coding exons of the PCSK1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Candidates for this test are patients with the non-syndromic form of monogenic obesity. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in PCSK1.

Gene

Official Gene Symbol OMIM ID
PCSK1 162150
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Proprotein Convertase 1/3 Deficiency AD,AR 600955

Citations

  • Albuquerque D. et al. 2015. Molecular Genetics and Genomics. 290: 1191-221. PubMed ID: 25749980
  • Creemers J.W. et al. 2012. Diabetes. 61: 383-90. PubMed ID: 22210313
  • Human Gene Mutation Database (Bio-base).
  • Pigeyre M. et al. 2016. Clinical Science. 130: 943-86. PubMed ID: 27154742

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×

ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

Total Price: $
×
Copy Text to Clipboard
×